The present invention relates to deoxy-1.4;3.6-dianhydrohexitol nitric acid esters having a vasodilative activity.
As hexitol derivatives having pharmacological activities, there are known isosorbide as a diuretic [The Merck Index, 11th edition, page 5113 (1989)] and isosorbide dinitrate as a coronary dilator [The Merck Index, 11th edition, page 5114 (1989)].
Further in connection with the present invention, 5-(4-methylpiperazin-1-yl)-5-deoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate showing a vasodilatory activity is disclosed in Japanese Published Unexamined Patent Application No. 58686/82 [U.S. Pat. No. 4,363,805 and EP-A-44940].
Organic nitrates, for example, nitroglycerine have been clinically used for angina pectoris. Because of poor oral absorption, however, it is impossible to use nitroglycerine for preventive therapy for attacks of angina pectoris and the administration of nitroglycerine is always limited to emergency care or attacks of angina pectoris in sublingual administration. On the other hand, it has been known that hexitol derivatives, e.g. isosorbide dinitrate are useful in the treatment of angina pectoris or coronary deficiency but its therapeutic effects were not enough in view of the pharmacological activities and side effects such as headache, vomiting, etc. In addition, they are explosive and should thus be handled carefully.